C. elegans CED-12 Acts in the Conserved CrkII/DOCK180/Rac Pathway to Control Cell Migration and Cell Corpse Engulfment

• Published in: Developmental cell Vol. 1; no. 4; pp. 491 - 502
• Main Authors: Wu, Yi-Chun, Tsai, Miao-Chih, Cheng, Li-Chun, Chou, Chung-Jung, Weng, Nei-Yin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2001
• Subjects: Amino Acid Sequence; Animals; Animals, Genetically Modified; Apoptosis - physiology; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Movement - physiology; Cloning, Molecular; Conserved Sequence; Cytoskeletal Proteins; Helminth Proteins - metabolism; Membrane Proteins - metabolism; Molecular Sequence Data; Mutation - physiology; Phagocytosis - physiology; Protein Kinases - metabolism; Proteins - metabolism; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-crk; rac GTP-Binding Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(01)00056-9

We have identified and characterized a novel C. elegans gene, ced-12, that functions in the conserved GTPase signaling pathway mediated by CED-2/CrkII, CED-5/DOCK180, and CED-10/Rac to control cell migration and phagocytosis of apoptotic cells. We provide evidence that ced-12 likely acts upstream of ced-10 during cell migration and phagocytosis and that CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro. We propose that the formation and localization of a CED-2-CED-5-CED-12 ternary complex to the plasma membrane activates CED-10, leading to the cytoskeletal reorganization that occurs in the polarized extension of cell surfaces in engulfing cells and migrating cells. We suggest that CED-12 counterparts in higher organisms regulate cytoskeleton dynamics, as CED-12 does in C. elegans.